Trimethylamine N-oxide (TMAO) is the organic compound in the class of amine oxides with the formula (CH3)3NO. This colorless solid is usually encountered as the dihydrate. It is a product of the oxidation of trimethylamine and a common metabolite in animals. It is an osmolyte found in saltwater fish, sharks, rays, molluscs, and crustaceans. It is a protein stabilizer that may serve to counteract urea, the major osmolyte of sharks, skates and rays. It is also higher in deep-sea fishes and crustaceans, where it may counteract the protein-destabilizing effects of pressure.[1] TMAO decomposes to trimethylamine (TMA), which is the main odorant that is characteristic of degrading seafood.

Trimethylaminuria is a defect in the production of the enzyme flavin containing monooxygenase 3 (FMO3).[4][5] Those suffering from trimethylaminuria are unable to convert choline-derived trimethylamine into trimethylamine oxide. Trimethylamine then accumulates and is released in the person's sweat, urine, and breath, giving off a strong fishy odor.

Studies published in 2013 indicate that high levels of TMAO in the blood are associated with an increased risk of major adverse cardiovascular events.[8] The concentration of TMAO in the blood increases after consuming foods containing carnitine[9] or lecithin[8] if the bacteria that convert those substances to TMAO are present in the gut.[10] High concentrations of carnitine are found in red meat, some energy drinks, and some dietary supplements; lecithin is found in soy, eggs,[10] as an ingredient in processed food and is sold as a dietary supplement. Some types of normal gut bacteria (e.g. species of Acinetobacter) in the human microbiome convert dietary carnitine to TMAO. TMAO alters cholesterol metabolism in the intestines, in the liver, and in artery wall. In the presence of TMAO, there is increased deposition of cholesterol in, and decreased removal of cholesterol from, peripheral cells such as those in the artery wall.[11]Vegan and vegetarian diets appear to select against gut flora that metabolize carnitine (in favor of other gut flora more coordinated with their food supply). This apparent difference in their microbiome is associated with substantially reduced gut bacteria capable of converting carnitine to TMAO.[9][12]

Another source of TMAO is dietary phosphatidylcholine, again by way of bacterial action in the gut. Phosphatidyl choline is present at high concentration in egg yolks and some meats.

It has been suggested that TMAO may be involved in the regulation of arterial blood pressure and aetiology of hypertension.[13]